AUTHOR=Kesler Shelli R. , Harrison Rebecca A. , Schutz Alexa De La Torre , Michener Hayley , Bean Paris , Vallone Veronica , Prinsloo Sarah 

TITLE=Strength of spatial correlation between gray matter connectivity and patterns of proto-oncogene and neural network construction gene expression is associated with diffuse glioma survival

JOURNAL=Frontiers in Neurology

VOLUME=Volume 15 - 2024

YEAR=2024

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2024.1345520

DOI=10.3389/fneur.2024.1345520

ISSN=1664-2295

ABSTRACT=Like other forms of neuropathology, gliomas appear to spread along neural pathways. Accordingly, our group and others have previously shown that brain network connecFvity is highly predicFve of glioma survival. In this study, we aimed to examine the molecular mechanisms of this relaFonship via imaging transcriptomics. We retrospecFvely obtained presurgical, T1-weighted MRI datasets from 669 adult paFents, newly diagnosed with diffuse glioma. We measured brain connecFvity using gray maVer networks and coregistered these data with a transcriptomic brain atlas to determine the spaFal co-localizaFon between brain connecFvity and expression paVerns for 14 proto-oncogenes and 3 neural network construcFon genes. We found that all 17 genes were significantly co-localized with brain connecFvity (p < 0.03, corrected). The strength of co-localizaFon was highly predicFve of overall survival in a cross-validated Cox ProporFonal Hazards model (mean area under the curve, AUC = 0.68 +/-0.01) and significantly (p < 0.001) more so for a random forest survival model (mean AUC = 0.97 +/-0.06). Bayesian network analysis demonstrated direct and indirect causal relaFonships among gene-brain co-localizaFons and survival. Gene ontology analysis showed that metabolic processes were overexpressed when spaFal co-localizaFon between brain connecFvity and gene transcripFon was highest (p < 0.001). Drug-gene interacFon analysis idenFfied 84 potenFal candidate therapies based on our findings. Our findings provide novel insights regarding how gene-brain connecFvity interacFons may affect glioma survival.